The present invention relates to the use of sordarin and derivatives thereof in controlling phytopathogenic fungi in crops; to agrochemical compositions containing the compounds; and to fermentation processes for the production of sordarin as well as the microorganisms used therein.
The control of phytopathogenic fungi is of great economic importance since fungal growth on plants or on parts of plants inhibits production of foliage, fruit or seed, and the overall quality of a cultivated crop. In fact, without crop protection, greater than 75% of the world""s food production would be lost. Even so, 12% is still lost to plant diseases. Because of the vast economic ramifications of fungal infection in agricultural and horticultural cultivations, a broad range of fungicidal and fungistatic products have been developed for general and specific applications. However, the widespread use of agricultural fungicides frequently induces resistance to currently available agents; thus, there exists a need to discover new antifungal compounds that are outside of the known chemical classes of agricultural fungicides, and/or act by a different mechanism than the available agents.
Sordarin (I, wherein Z is (d)) is an antifungal antibiotic isolated from the ascomycete Sordaria araneosa (see GB 1,162,027 and Helvetica Chimica Acta, 1971, 51:119-20). Other compounds having the sordarin skeleton have also been reported as antifungal agents. Japanese Kokai J62040292 discloses the compound zofimarin (I, wherein Z is (e)) isolated from Zopfiela marina sp.; Japanese Kokai J06157582 discloses the compound BE-31405 (I, wherein Z is (f) and Ra is acetyl) isolated from Penicillium sp.; and SCH57404 (I, wherein Z is (f) and Ra is methyl) is reported in J. Antibiotics, 1995, 48:1171-1172. Semi-synthetic sordarin derivatives are reported in PCT Applications WO96/14326 and WO96/14327. While the aforementioned compounds all have been referred to as antifungal agents, the only uses mentioned in the literature have been for treatment of human and/or animal mycotic diseases. There is no teaching or suggestion that sordarin and derivatives thereof are effective against phytopathogenic fungi, or that they are suitable for agricultural applications.
The present invention provides in one aspect a method for controlling phytopathogenic fungi which comprises administering to a plant in need of such control an antifungal effective amount of a compound of formula (I) 
and wherein Z is a tetrahydropyrano group selected from 
and salts and solvates (e.g. hydrates) or metabolically labile derivatives thereof, wherein
Ra is OC(O)CH3 or CH3;
R1 is hydrogen, halogen, hydroxyl, C1-4alkoxy or acyloxy;
R2 and R3 may each independently represent hydrogen, C1-6alkyl or C1-4alkoxy C1-4alkyl, or
R2 and R3 may together with the carbon atom to which they are attached represent Cxe2x95x90O, Cxe2x95x90S or C3-8cycloalkyl;
R4 is hydrogen or CH2R7 (where R7 is hydrogen, hydroxyl, C1-4alkoxy or a group OCOR8 in which R8 is C1-4alkyl or aryl);
R5 and R6 may each independently represent hydrogen, C1-6alkyl or C1-4alkoxy C1-4alkyl, or
R5 and R6 may together with the carbon atom to which they are attached represent Cxe2x95x90O, Cxe2x95x90S or C3-8cycloalkyl; n is zero or 1;
X and Y may each independently represent oxygen, sulfur or CR9R10 (where R9 and R10 may each independently represent hydrogen, C1-6alkyl, C1-4alkoxy or C1-4alkoxyC1-4alkyl or R9 and R10 may together with the carbon atom to which they are attached represent Cxe2x95x90O, Cxe2x95x90S, C3-8cycloalkyl or Cxe2x95x90CHR11 where R11 represents hydrogen or C1-4alkyl); or when X or Y is oxygen and n is zero then xe2x80x94Yxe2x80x94CR2R3 or xe2x80x94Xxe2x80x94CR2R3xe2x80x94 respectively may also represent xe2x80x94Nxe2x95x90CR3xe2x80x94 or xe2x80x94NR12xe2x80x94CR2R3xe2x80x94(where CR2 and R3 are Cxe2x95x90O and R12 is C1-4alkyl an acyl group COR13 where R13 is C1-6alkyl) or when Y is oxygen and n is zero X may be represent the group CR11 (wherein R11 has the meanings defined above) which is attached to the pyran ring by a double bond;
R15 is hydrogen, halogen, azido, C1-6alkyl, hydroxy, C1-6alkoxy (optionally substituted by 1 or 2 hydroxy or a ketal thereof or 1 or 2 C1-3alkoxy groups), arylC1-4alkoxy, C3-6alkenyloxy, a group OCOR18 (where R18 is arylC1-4alkoxy or a C1-10alkyl group optionally containing one or two double bonds) or C1-6alkoxycarbonyl C1-4alkoxy, and R16 represents hydrogen or R15 and R16 may together with the carbon atom to which they are attached represent Cxe2x95x90O or Cxe2x95x90CH2;
R17 is CH2R19 where R19 is hydrogen, hydroxyl, C1-4alkoxy or a group OCOR20 in which R20 is C1-4alkyl); and
W is oxygen, sulfur, or CH2; and the dotted line in group (a) indicates the optional presence of an additional bond;
R1a is hydrogen, halogen, hydroxyl or C1-4alkoxy;
R2a hydrogen, halogen, hydroxyl, C1-10alkoxy, C1-10alkylthio, C1-6alkoxyC1-4alkoxy, arylC1-6alkyloxy, arylC3-6alkenyloxy, azido, NR5a COR5a (where each R5a is independently hydrogen or C1-6alkyl), OR6a (where R6a is a cyclic ether containing 4 to 8 atoms linked to the oxygen atom via a ring carbon atom adjacent to the ring oxygen atom) or a group YaC(xe2x95x90O) xe2x80x94Xaxe2x80x94R7a where Ya is oxygen, sulfur or NH, Xa is either a bond, an oxygen atom or a moiety NR8a in which R8a is hydrogen or C1-6alkyl, and R7a is C1-10alkyl optionally containing one or two double bonds, aryl, arylC1-4alkyl, arylC2-4alkenyl, haloC1-6alkyl, or C1-6alkoxyC1-4alkyl), and R3a represents hydrogen, or
R2a and R3a may together with the carbon atom to which they are attached represent Cxe2x95x90O or Cxe2x95x90NOR9a (where R9a is C1-6alkyl); and
R4a is hydroxyl, C1-6alkoxy or OC(xe2x95x90O)R7a (where R7a is as defined above); with the proviso that when R1a represents a hydroxyl group in the axial configuration and R4a is methoxy then R2a cannot represent a group in the axial configuration selected from hydroxyl and OCOCHCHZxe2x95x90CHxe2x80x94CHExe2x95x90CHCH3.
In another aspect the present invention provides an agricultural composition for use in controlling phytopathogenic fungi which comprises an antifungal effective amount of a compound of formula I and an agriculturally acceptable carrier.
Another aspect of the present invention provides a process for the production of sordarin which comprises:
cultivating a sordarin producing strain of Rosellinia subiculata in a nutrient medium containing assimilable sources of carbon and nitrogen; and
isolating sordarin.
Another aspect of the present invention provides a biologically pure culture of Rosellinia subiculata having the identifying characteristics of ATCC 74386.
A further aspect of the present invention provides a process for the production of sordarin which comprises:
cultivating a sordarin producing strain of a fungus having the identifying characteristics of ATCC 74387 in a nutrient medium containing assimilable sources of carbon and nitrogen; and
isolating sordarin.
Another aspect of the present invention provides a biologically pure culture of a fungus having the identifying characteristics of ATCC 74387.
In the application, unless otherwise specified, the following definitions apply:
The term xe2x80x9ccontrolxe2x80x9d or xe2x80x9ccontrollingxe2x80x9d includes prophylactic use (i.e. to protect against infection) and curative use (i.e. to eradicate infection).
The term xe2x80x9cplantsxe2x80x9d include whole live plants or parts thereof, foliage, flowers, seeds, fruits, and other materials derived from plants. The term also includes roots of the plant via application of the active ingredient to the soil.
The term xe2x80x9ccompositionxe2x80x9d, as in agricultural or agrochemical composition, is intended to encompass a product comprising the active ingredient(s), and the inert ingredient(s) that make up the carrier, as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the ingredients, or from dissociation of one or more of the ingredients, or from other types of reactions or interactions of one or more of the ingredients. Accordingly, the compositions of the present invention encompass any composition made by admixing a compound of the present invention and an agriculturally acceptable carrier.
xe2x80x9cAlkylxe2x80x9d as a group or part of a group means a straight or branched chain alkyl moiety such as methyl, ethyl, n-propyl, n-butyl, isopropyl, s-butyl, t-butyl, n-hexyl and n-octyl.
xe2x80x9cArylxe2x80x9d as a group or part of a group means phenyl or heteroaryl each optionally substituted by one to three groups independently selected from halogen, hydroxyl, C1-6alkyl, C1-6alkoxy or C1-4alkoxycarbonyl. The heteroaryl group may be a 5- or 6-membered heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen and sulfur. Suitable examples of heteroaryl groups include pyridyl, furyl, thienyl and pyrrolyl.
xe2x80x9cHalogenxe2x80x9d or xe2x80x9chaloxe2x80x9d means fluorine, chlorine, bromine or iodine.
When R1 is an acyloxy group it may represent, for example a group OCOR13 where R13 is as defined above.
Suitable salts of a compound of formula I include inorganic base salts such as alkali metal salt (e.g. sodium and potassium salts), ammonium salts, and organic base salts. Suitable organic base salts include amine salts such as trialkylamine (e.g. triethylamine), dialkylamine salts (e.g. dicyclohexylamine), optionally substituted benzylamine (e.g. phenylbenzylamine or p-bromobenzylamine), ethanolamine, diethanolamine, N-methylglucosamine, N-methylpiperidine, pyridine and substituted pyridine (e.g. collidine, lutidine, 4-dimethylaminopyridine), and tri(hydroxymethyl)methylamine salts, and amino acid salts (e.g. lysine or arginine salts).
Metabolically labile derivatives of compounds of formula I are compounds which are converted in the subject being treated (be it the plant, foliage, flower, fruit, seed, or other parts or product of the plant, or the soil) into compounds of formula I. Examples of such derivatives include conventional metabolically labile esters formed from the carboxylic acid in the molecule.
In one preferred embodiment the compound of formula I is sordarin.
In another preferred embodiment, the phytopathogenic fungi being controlled are Erysiphe spp. (powdery mildew) and other powdery mildews such as, Sphaerotheca spp, Podosphaera spp., and Uncinula spp.; Puccinia spp. (rusts); Rhizoctonia spp; Ustilago spp. (smut); Venturia spp. (scab) Helminthosporium spp. (Curvularia, Drechslera, Exserohilum spp.); Stagnospora spp.; Septoria spp.; Botrytis spp. (gray mold); Cercospora spp.; Pseudocercosporella spp.; Pyricularia spp.; Phytophthora spp.; Fusarium spp; Verticillium spp.; Plasmopara spp.; Alternaria spp.
The more preferred embodiment of these phytopathogenic fungi being controlled are Erysiphe graminis, Puccinia recondita, Stagnospora nodorum, Septoria tritici, Pyricularia oryzae, Phytophthora infestans, Plasmopara viticola and Botrytis cinerea. 
In another embodiment, the plants treated are: cereal crops (e.g. wheat, rye, oat, barley, rice, sorghum and related crops); beet (sugar beet and fodder beet); pomes, dropes and soft fruit (e.g. apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries, and blackberries); leguminous plants (e.g. beans, peas, lentils and soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans and groundnuts); curcubits (e.g. cucumber, squash, and melon); fiber plants (e.g. cotton, flax, hemp, and jute); citrus fruit (e.g. oranges, lemons, mandarins and grapefruit); vegetables (e.g. lettuce, cabbage, spinach, carrot, asparagus, paprika, onions, tomatoes, and potatoes); Lauraceae: (avocados, cinnamon and camphor); or plants such as maize, tobacco, nuts, coffee, sugar cane, tea, vines, hops, bananas and natural rubber plants, as well as ornamentals (flowers, shrubs, broad-leaved trees and evergreens, such as conifers).
Preparation of Compounds. Compounds of formula I are all known compounds and methods for their preparation are available in the literature.
Sordarin (I, wherein Z is (d)) can be obtained by the cultivation of Sordaria araneosa NRRL 3196 (also deposited with the ATCC as ATCC 36386) according to the procedure described in GB1,162,027 or in WO96/14326. Sordarin can also be isolated from the fermentation of Rosellinia subiculata and an unidentified fungus ATCC 74387 as described hereinbelow.
Zofirmarin (I, wherein Z is (e)) may be obtained from the fermentation broth of Zofiela marina SANK 21274 (ATCC 34456) as described in Japanese Kokai 62040292. BE31405 (I, wherein A is (f) and Ra is acetyl) is produced by Penicillum sp. F31405 as described in Japanese Kokai 06157582. SCH57404 (I, wherein A is (f) and Ra is methyl) is produced by a fungus identified as Schering culture number SCF1082A as reported in J. Antibiotics, 1995, 48(10):1171-1172.
Sordarin derivatives (I, wherein Z is (a) or (b)), and their preparation are described in PCT Application WO96/14326; and sordarin derivatives (I, wherein Z is (c)) and their preparation are described in PCT Application WO96/14327.
As mentioned above, two other organisms have been found to produce sordarin.
One of the fungal strains used to produce sordarin is an unidentified sterile fungus GB3109 that was isolated from the internal tissues of roots of a mangrove shrub, Conocarpus erectus (Combretaceae), collected in the Manglar de Rxc3xado Rincxc3x3n, Penxc3xadnsula de Osa, Provincia de Puntarenas, Costa Rica, and identified as MF6232 in the culture collection of Merck and Co., Inc., Rahway, N.J. This culture was deposited on Aug. 27, 1996 in the permanent collection at the American Type Culture Collection, 12301 Parklawn Drive, Rockville, Md. 20852, USA under the terms of The Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure, and assigned the accession number ATCC 74387.
The fungus was grown on a variety of mycological media, under different light regimes, and on sterilized leaves and filter paper but in all cases, it has failed to produce reproductive structures and thus cannot be identified.
In agar culture, colonies of the fungus exhibit the following morphology:
Colonies on oatmeal agar (Difco) at 23xc2x0 C., 12 hr photoperiod, growing moderately fast, attaining 85-90 mm in 14 days, with advancing zone appressed, even, obscurely zonate, strongly radially striate, with moist appressed mycelium at the center, becoming silky with radiating prostrate hyphal bundles or strands, translucent to pale pink, near Pale Ochraceous Salmon (capitalized color names from Ridgway, R. 1912. Color Standards and Nomenclature, Washington, D.C.), Light Ochraceous Salmon, pinkish gray Avellaneous, Cinnamon-Drab, or white in uppermost aerial mycelium, reverse pale pinkish gray, exudates absent, odor faintly fragrant. No growth at 37 C on oatmeal agar.
Colonies on V8 juice agar (Stevens, R. B. 1981. Mycology Guidebook. University of Washington Press, Seattle, pg. 665) at 23xc2x0 C., 12 hr photoperiod, growing slowly attaining 37-42 mm in 14 days, submerged to at the margin, mostly with appressed most mycelium, with some scant floccose aerial mycelium towards outer third, zonate, translucent to pale grayish pink, similar to color on oatmeal agar, reverse translucent to pale reddish brown, near Wood Brown, Fawn Color.
Colonies on cornmeal agar (Difco) at 25xc2x0 C., 12 hr photoperiod, growing slowly, attaining 33-34 mm in 14 days, with margin submerged, lacking aerial hyphae, zonate, translucent.
The mycelium is composed of highly branched, simple septate, hyaline hyphae.
The second fungal strain (GB3719) used to produce sordarin is a strain of Rosellina subiculata (Ascomycotina, Xylariaceae), designated as MF6239 in the culture collection of Merck and Co., Inc., Rahway, N.J. This culture was deposited on Aug. 27, 1996 in the permanent collection at the American Type Culture Collection, 12301 Parklawn Drive, Rockville, Md. 20852, USA under the terms of The Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure, and assigned the accession number ATCC 74386.
Ascomata of Rosellinia subiculata (GB3719) were found on a decorticated hardwood limb on the shore of the Navesink River, Monmouth Co., N.J. In the laboratory, the apices of several ascomata were removed with a sterilized microtome blade and asci, paraphyses and ascospores from the centrum were removed with an insect pin and streaked onto malt-yeast extract agar. Ascospores were incubated overnight until they germinated and were transferred to tubes of malt-yeast extract agar to initiate pure colonies.
The morphology of Rosellinia subiculata (GB3719) generally conformed to descriptions in the literature (J. B. Ellis and B. M. Everhart. 1892. The North American Pyrenomycetes. Published by the authors, Newfield, N.J. pg. 165-166; L. E. Petrini. 1993. Rosellinia species of the temperate zones. Sydowia 44:169-281). The key features that lead to identification of the fungus as Rosellinia subiculata were: stromatic ascomata occurring singly but aggregated or fused in small clusters on a mycelial subiculum on decorticated wood; stromata were hemispherical, papillate, smooth, shiny, black, subiculum a thin mycelial mat, pale buff, or sometimes appearing only as a lightly colored discoloration of the wood adjacent to the stromata; asci were cylindrical with an amyloid apical plug; ascospores were brownish gray, broadly elliptical to slightly reniform, smooth, without appendages or sheaths, with a straight, ventral germ slit, 10-12xc3x975-6 xcexcm.
In agar culture, colonies of the fungus exhibit the following morphology:
Colonies on oatmeal agar at 23xc2x0 C., 12 hr photoperiod, growing moderately fast, attaining 73-75 mm in 14 days, with advancing zone appressed, even, obscurely zonate, with white velvety to floccose mycelium over inner third, with moist appressed mycelium over outer two-thirds, translucent to white or pale pink, pale vinaceous pink, Light Vinaceous Cinnamon in reverse, exudates absent, slightly fragrant odor. No growth at 37 C on oatmeal agar.
Colonies on V8 juice agar at 23xc2x0 C., 12 hr photoperiod, growing slowly attaining 25-35 mm in 14 days, submerged at the margin, mostly with appressed most mycelium, with some floccose aerial mycelium towards inner third, zonate, translucent to pale grayish pink, Vinaceous Cinnamon, reverse translucent to cinnamon, Orange-Cinnamon, Cinnamon, or pale reddish brown, Russet, Fawn Color, odor fragrant.
Colonies on cornmeal agar at 25xc2x0 C., 12 hr photoperiod, growing slowly, attaining 29-34 mm in 14 days, with margin submerged, lacking aerial hyphae, azonate, translucent, or with scant white mycelium at inoculation point, colorless in reverse.
When first grown in culture in August of 1993, the strain produced scant conidiophores and conidia of a Geniculosporium anamorph similar to that described by Petrini 1993. However, sporulation is no longer apparent, most likely due to prolonged storage and repeated transfers. At least in one case, a few mature perithecia with asci and ascospores identical to those observed in nature were formed after 5 weeks growth on oatmeal agar. Ascospores germinated overnight when incubated on malt-yeast extract agar at room temperature. The mycelium is composed of highly branched, simple septate, hyaline hyphae.
Sordarin is produced by cultivating a strain of Rosellina subiculata or the unidentified fungus MF6232 (ATCC74387) capable of producing said compound on a conventional solid medium or in a conventional aqueous medium. The organism is grown in a nutrient medium containing known nutritional sources for similar fungi, i.e. assimilable sources of carbon and nitrogen plus optional inorganic salts and other known growth factors. The general procedures used for the cultivation of other similar fungi are applicable to the present invention.
The nutrient medium should contain an appropriate assimilable carbon source such as ribose, glucose, sucrose, cellobiose or fructose. As nitrogen source, ammonium chloride, ammonium sulfate, urea, ammonium nitrate, sodium nitrate, etc. may be used either alone or in combination with organic nitrogen sources such as peptone, fish meal extract, yeast extract, corn steep liquor, soybean powder, cotton seed flour, etc. There may also be added, if necessary, nutrient inorganic salts to provide sources of sodium, potassium, calcium, ammonium, phosphate, sulfate, chloride, bromide, carbonate, zinc, magnesium, manganese, cobalt, iron, and the like.
Production of sordarin may be effected at any temperature conducive to satisfactory growth of the producing organism, e.g. 30xc2x0 C. Ordinarily, optimum production of the desired compound is obtained in shake flasks after incubation periods of 7-21 days. Aeration in shake flasks is achieved by agitation, e.g. shaking on a rotary shaker. If fermentation is to be carried out in tank fermentors, it is desirable to produce a vegetative inoculum in a nutrient broth by inoculating the broth culture from slant culture, lyophilized culture or frozen culture of the organism. After obtaining an active inoculum in this manner, it is aseptically transferred to the fermentation tank medium. Production of the desired compound in tank fermentors usually reaches the optimum after 7 to 21 days of incubation. Agitation in the tank fermentor is provided by stirring and aeration may be achieved by injection of air or oxygen into the agitated mixture. Compound production may be monitored using chromatographic or spectroscopic techniques, or by a conventional biological assay.
In a preferred embodiment, the producing strain is Rosellina subiculata having the identifying characteristics of ATCC 74386, or a mutant or a variant thereof.
In another preferred embodiment, the producing strain of the unidentified fungus is ATCC 74387.
Sordarin is readily recovered from fermentation broth by extracting the whole broth with an organic solvent such as methyl ethyl ketone. The compounds may be purified using standard methods well known in the art such as gel filtration chromatography, thin layer chromatography, high performance liquid chromatography, concentration, precipitation and/or crystallization, or combinations thereof. Alternatively, the whole broth or an organic extract thereof may be spray-dried or freeze-dried, followed by purification as above mentioned.
Utility. Compounds of formula I have use as broad spectrum crop antifungal agents and are extremely effective on a broad spectrum of phytopathogenic fungi, in particular those from the following classes (consisting of): Deuteromycetes (e.g. Botrytis spp., Septoria spp., Pyricularia spp., Stagnospora spp., Helminthosporium spp. (Curvularia, Drechslera, Exserohilum spp.), Fusarium spp., Cercospora spp., Rhynchosporium, spp. Pseudocercosporella, spp. and Alternaria spp.); Basidiomycetes (e.g. Puccinia spp., Rhizoctonia spp., and Hemileia); Ascomycetes (e.g. Venturia spp., Podospharera spp., Erysiphe spp., Monilinia spp. and Uncinula spp.); and Oomycetes (e.g. Phytophthora spp., Pernospora spp., Bremia spp., Pythium spp., and Plasmopara spp.). The foregoing list exemplifies the phytopathogenic fungi against which the named compounds demonstrate activity, and is not limiting in any manner. These compounds have very advantageous curative, preventive and systemic fungicidal properties for protecting plants, and can be used to inhibit or to destroy the microorganisms occurring on plants or on parts of plants (the fruit, blossom, leaves, stalks, tubers or roots) of different crops of useful plants, while at the same time parts of plants that grow later are also protected against such microorganisms. They can also be used as dressings in the treatment of plant propagation material, especially seed (fruit, tubers, grain) and plant cuttings (for example rice), to provide protection against fungal infections and against phytopathogenic fungi occurring in the soil. Compounds of formula I of the invention are distinguished by the fact that they are especially well tolerated by plants and are environmentally friendly.
Based on the spectrum of activity, the compounds of the present invention can be used to protect or cure plants of phytopathogenic fungi affecting various useful crops. The following species of plants are suitable for the use described in the scope of the invention of the stated compounds: cereal (e.g. wheat, rye, oat, barley, rice, sorghum and related crops); beet (sugar beet and fodder beet); pomes, dropes and soft fruit (e.g. apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries, and blackberries); leguminous plants (e.g. beans, peas, lentils and soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans and groundnuts); curcubits (e.g. cucumber, squash, and melon); fiber plants (e.g. cotton, flax, hemp, and jute); citrus fruit (e.g. oranges, lemons, mandarins and grapefruit); vegetables (e.g. lettuce, cabbage, spinach, carrot, asparagus, paprika, onions, tomatoes, and potatoes); Lauraceae: (avocados, cinnamon and camphor); or plants such as maize, tobacco, nuts, coffee, sugar cane, tea, vines, hops, bananas and natural rubber plants, as well as ornamentals (flowers, shrubs, broad-leaved trees and evergreens, such as conifers). However, the aforementioned plant species do not constitute a limiting list of plants with respect to spectrum by the stated compounds.
The compounds of formula I are particularly useful for controlling the following plant diseases:
Erysiphe graminis (powdery mildew) on wheat, barley, oat, rye and turf and other powdery mildews on various hosts such as, Erysiphe cichoracearum and Sphaerotheca fuliginea on cucurbits, Podosphaera leucotricha on apples, Uncinula necator on vines; Puccinia species (rusts) on wheat, barley and other hosts; Rhizoctonia solani in cotton, Ustilago species (smut) in cereals and sugar cane, Venturia inaequalis (scab) in apples, Helminthosporium (Curvularia, Drechslera, Exserohilum) species in cereals, Stagnospora nodorum and Septoria tritici in wheat, Botrytis cinerea (gray mold) in strawberries and grapes, Cercospora arachidicola in groundnuts, Pseudocercosporella herpotrichoides in wheat and barley, Pyricularia oryzae in rice, Phytophthora infestans in potatoes and tomatoes, Fusarium and Verticillium species in various plants, Plasmopara viticola in grapes, Alternaria species in fruit and vegetables. The compounds of formula I may also be used for protecting materials (e.g. preservation of timber against Paecilomyces variotii).
Agrochemical Compositions. The compounds of formula I can be used in either an unmodified form or preferably together with adjuvants conventionally employed in the art of agrochemical formulation and are for this purpose forms known mainly as: emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute solution, suspensions (including high-percentage aqueous, oily or other suspensions), dispersions, oil dispersions, broadcasting agents, wettable powders, soluble powders, dusts, granules, and encapsulations. The formulations are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredients with extenders, e.g. solvents, solid carriers and, where appropriate, surface-active compounds (surfactants). Powders, dusts and broadcasting agents may be prepared by mixing or grinding the active ingredients with a solid carrier. Granules, e.g., coated, impregnated or homogeneous granules, may be prepared by bonding the active ingredients to solid carriers.
Suitable solvents are: aromatic hydrocarbons, preferably the fractions containing 8 to 12 carbon atoms, such as xylene mixtures or substituted naphthalenes, chlorinated aromatics such as chlorobenzenes, phthalates, such as dibutyl or dioctyl phthalate, aliphatic hydrocarbons, such as cyclohexane or paraffins, alcohols and glycols and their ethers and esters, such as ethanol, ethylene glycol, ethylene glycol monomethyl or monoethyl ether, ketones such as cyclohexanone, amines such as ethanolamine, strongly polar solvents, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, and vegetable oils or epoxidised vegetable oils, such as epoxidised coconut oil or soybean oil; and water.
Examples of surfactants are: alkali metal, alkaline earth metal and ammonium salts of aromatic sulfonic acids, e.g., ligninsulfonic acid, phenolsulfonic acid, naphthalenesulfonic acid and dibutylnaphthalenesulfonic acid, and of fatty acids, alkyl and alkylaryl sulfonates, and alkyl, lauryl ether and fatty alcohol sulfates, and salts of sulfated hexadecanols, heptadecanols, and octadecanols, salts of fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and naphthalene derivatives with formaldehyde, condensation products of naphthalene or naphthalenesulfonic acids with phenol and formaldehyde, polyoxyethylene octylphenol ethers, ethoxylated isooctylphenol, ethoxylated octylphenol and ethoxylated nonylphenol, alkylphenol polyglycol ethers, tributylphenyl polyglycol ethers, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers, ethoxylated polyoxypropylene, lauryl alcohol polyglycol ether acetal, sorbitol esters, lignin-sulfite waste liquors and methyl cellulose.
Examples of solid carriers are mineral earths such as silicic acids, silica gels, silicates, talc, kaolin, attapulgus clay, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, aluminas calcium sulfate, magnesium sulfate, magnesium oxide, ground plastics, fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate, and ureas, and vegetable products such as grain meals, bark meal, wood meal, and nutshell meal, cellulosic powders, etc.
Compounds of formula I may be mixed and applied together with other active ingredients, for example herbicides, insecticides, bactericides, nematocides, molluscicides, growth regulators, micronutrients, and fertilizers. The other ingredients may also be one or more fungicides belonging to but not restricted to the following classes of fungicides: carboxamides, benzimidazoles, triazoles, hydroxypyridines, dicarboxamides, phenylamides, thiadiazoles. carbamates, cyano-oximes, cinnamic acid derivatives, morpholines, imidazoles, xcex2-methoxy acrylates and pyridines/pyrimidines. Furthermore, these additional active ingredients may be used as mixtures of several of the preparations, if desired together with other application promoting adjuvants usually used in the art of formulation. Suitable carriers and adjuvants can be solid or liquid and correspond to the substances typically used in formulation technology (e.g. natural or regenerated mineral substances, solvents, disperants, and wetting agents).
The following list of fungicides with which compounds of formula I may be combined is intended to illustrate possible combinations but not to impose any restrictions. Examples of fungicides which may be combined with compounds of formula I are: sulfur, dithiocarbamates and their derivatives, such as ferric dimethyldithiocarbamate, zinc dimethyldithiocarbamate, zinc ethylenebisdithiocarbamate, manganese ethylenebisdithiocarbamate, manganese zinc ethylenediaminebisdithiocarbamate, tetramethylthiuram disulfides, ammonia complex of zinc N,Nxe2x80x2-ethylenebisdithiocarbamate, ammonia complex of zinc N,Nxe2x80x2-propylenebisdithiocarbamate, zinc N,Nxe2x80x2-propylenebisdithiocarbamate and N,Nxe2x80x2-polypropylenebis (thiocarbamyl) disulfide; nitro derivative, such as dinitro(1-methylheptyl)-phenyl crotonate, 2-sec-butyl-4,6-dinitrophenyl 3,3-dimethylacrylate,2-sec-butyl-4,6-dinitrophenyl isopropylcarbonate and diisopropyl 5-nitroisophthalate; heterocyclic substances, such as 2-heptadecylimidazol-2-yl acetate, 2,4-dichloro-6-(o-chloroanilino)-s-triazine, O,O-diethyl phthalimidophosphonothioate, 5-amino-1-[bis-(dimethylamino)-phosphinyl]-3-phenyl-1,2,4-triazole, 2,3-dicyano-1,4-dithioanthraquinone, 2-thio-1,3-dithio[4,5-b]quinoxaline, methyl 1-(butylcarbamyl)-2-benzimidazolecarbamate, 2-methoxycarbonylaminobenzimidazole, 2-(fur-2-yl)-benzimidazole, 2-(thiazol-4-yl)benzimidazole, N-(1,1,2,2-tetrachloroethylthio)-tetrahydrophthalimide, N-trichloromethylthiotetrahydrophthalimide, N-trichloromethylthiophthalimide, N-dichlorofluoromethylthio-Nxe2x80x2,Nxe2x80x2-dimethyl-N-phenylsulfuric acid diamide, 5-ethoxy-3-trichloromethyl-1,2,3-thiadiazole, 2-thiocyanatomethylthiobenzothiazole, 1,4-dichloro-2,5-dimethoxybenzene, 4-(2-chlorophenylhydrazono)-3-methyl-5-isoxazolone, 2-thiopyridine 1-oxide, 8-hydroxyquinoline and its copper salt, 2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiyne, 2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiyne 4,4-dioxide, 2-methyl-5,6-dihydro-4H-pyran-3-carboxanilide, 2-methylfuran-3-carboxanilide, 2,5-dimethylfuran-3-carboxanilide, 2,4,5-trimethylfuran-3-carboxanilide, 2,5-dimethyl-N-cyclohexylfuran-3-carboxamide, N-cyclohexyl-N-methoxy-2,5-diethylfuran-3-carboxamide, 2-methylbenzanilide, 2-iodobenzanilide, N-formyl-N-morpholine-2,2,2-trichloroethylacetal, piperazine-1,4-diylbis-(1-(2,2,2-trichloroethyl)-formamide), 1-(3,4-dichloroanilino)-1-formylamino-2,2,2-trichloroethane, 2,6-dimethyl-N-tridecylmorpholine and its salts, 2,6-dimethyl-N-cyclododecylmorpholine and its salts, N[3-(p-tert.-butylphenyl)-2-methylpropyl]-cis-2,6-dimethylmorpholine, N-3-(p-tert.-butylphenyl)-2-methylpropyl]-piperidine, 1-2-(2,4-dichlorophenyl)-4-ethyl-1,3-dioxolan-2-yl-ethyl]-1H-1,2,4-triazole, 1-[2-(2,4-dichlorophenyl)-4-n-propyl-1,3-dioxolan-2-yl-ethyl]-1H-1,2,4-triazole, N-(n-propyl)-N-(2,4,6-trichlorophenoxyethyl)-N]-imidazolylurea, 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)-butan-2-one, 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)-butan-2-ol, alpha-(2-chlorophenyl)-alpha-(4-chlorophenyl)-5-pyrimidinemethanol, 5-butyl-(2-dimethylamino-4-hydroxy-6-methylpyrimidine, bis-(p-chlorophenyl)-3-pyridinemethanol, 1,2-bis-(3-ethoxycarbonyl-2-thioureido)-benzene, 1,2-bis-(3-methoxycarbonyl-2-thioureido)-benzene, and various fungicides, such as dodecylguanidine acetate, 3-[3-(3,5-dimethyl-2-oxycyclohexyl)-2-hydroxyethyl]-glutaramide, hexachlorobenzene, DL-methyl-N-(2,6-dimethylphehyl)-N-fur-2-yl alanate, methyl DL-N-(2,6-dimethylphenyl)-N-(2]-methoxyacetyl)-alanate, N-(2,6-dimethylphenyl)-N-chloroacetyl-DL-2-aminobutyrolactone, methyl DL-N-(2,6-dimethylphenyl)-N-(phenylacetyl)-alanate, 5-methyl-5-vinyl-3-(3,5-dichlorophenyl)-2,4-dioxo-1,3-oxazolidine, 3-[3,5-dichlorophenyl]-5-methyl-5-methoxymethyl-1,3-oxazolidine-2,4-dione, 3-(3,5-dichlorophenyl)-1-isopropylcarbamylhydantoin, N-(3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximide, 2-cyano-[N-(ethylaminocarbonyl)-2-methoximino]-acetamide, 1-[2-(2,4-dichlorophenyl)-pentyl]-1H-1,2,4-triazole, 2,4-difluoro-a-(1H-1,2,4-triazol-1-ylmethyl)-benzhydryl alcohol, N-(3-chloro-2,6-dinitro-4-trifluoromethylphenyl)-5-trifluoromethyl-3-chloro-2-aminopyridine, and 1-((bis-(4-fluorophenyl)-methylsilyl)-methyl)-1H-1,2,4-triazole.
Method of Use. As with the nature of compositions, the method of application such as spraying, atomizing, dusting, scattering, coating, dressing, and pouring are chosen in accordance with the intended objectives of the application and the prevailing circumstances. One method of applying the active ingredient or agrochemical composition containing at least one of the stated compounds is application to the plants (i.e. foliar application). However, the active ingredient can also penetrate the plant through the roots via the soil (i.e. soil application). This may be in the form of either a liquid application to the soil (drench) or a granular application.
The active ingredient can also be applied to plant propagation material such as seeds (fruits, tubers or grains) or plant cuttings, in either liquid form (coating) or in solid form (dressing). Seeds, for example, can be dressed before sowing. The compounds of the invention can also be applied to grains either by impregnating the grains with a liquid formulation of by coating them with a solid formulation. The composition can also be applied to the locus of planting when planting the propagation material, for example to the seed furrow during sowing.
Advantageous rates of application are normally from 50 g to 50 kg of active ingredient (a.i.) per hectare, preferably 100 g to 2 kg a.i./ha, most preferably 100 g to 600 g a.i./ha. The active ingredients of the stated compounds are typically used in the form of compositions and can be applied to the plant, or to parts of the plant either simultaneously or in succession with further active ingredients. These further active ingredients can be fertilizers, additional micronutrients, or other plant growth affecting compounds. They can, however, also be selective herbicides, insecticides, bactericides, nematocides, insecticides, and molluscicides,as well as other fungicides.